Induced Pluripotent Stem Cell (iPSC)–Derived Lymphocytes for Adoptive Cell Immunotherapy: Recent Advances and Challenges

In the rapidly developing field of adoptive cell immunotherapy, there is urgent need for discoveries that would improve outcomes, extend the applicability, and reduce the costs. Induced pluripotent stem cells (iPSC) can be a source of broadly applicable cellular immunotherapeutics, which have been manufactured, validated, and banked in advance, and can be applied across HLA barriers. Here, we discuss the recent advances and challenges in the generation of iPSC-derived cellular products for cancer therapy. iPSCs can be differentiated to functional tumor-specific T and NK cells in vitro with demonstrable in vitro and in vivo anti-tumor activity. Genetic modifications employed at the iPSC level can deliver desirable immunotherapeutic attributes to the generated immune effectors. iPSC-NK cells are currently evaluated in a clinical setting and pre-clinical testing of iPSC-T cells shows promising results but their production seems more challenging. The use of iPSCs for the generation of tumor-targeting T/NK cells constitutes a feasible strategy to overcome limitations in manufacturing, efficacy, and applicability of cellular therapeutics.